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25.6.11

Fish Oils and Heart Disease : A Closer Look
Dozens of randomized, controlled trials have tested the effect of fish oil supplementation and increases in the intake of fatty fish on total and cardiovascular mortality. Virtually all of them have been conducted in people with established heart disease taking drugs such as statins and aspirin, and most of them have lasted fewer than two years. In 2004, the Cochrane Collaboration published a massive review and meta-analysis of these trials.79 Meta-analyses pool the data of many studies together in an attempt to show the big picture and test whether methodological differences between trials or random chance are more likely to account for differences in results. When the authors pooled the data from forty-eight trials lasting longer than six months, the only effect that could be distinguished from chance was a reduced risk of heart failure. Fish oil provided no reduction in total or cardiovascular mortality.
Trials lasting less than one year were most likely to show positive results, while the only trial lasting more than four years—the Diet and Reinfarction 2 (DART 2) trial—showed a 15 percent increase in total mortality and a 30 percent increase in cardiovascular mortality. DART 2 used dietary advice to increase fatty fish intake in addition to fish oil supplementation, so could not be placebo-controlled or double-blind, and unfortunately funding problems led to interruptions of the recruitment process in the middle of the trial. Nevertheless, with over three thousand participants it was one of the largest fish oil trials ever conducted and, with over four years follow-up, it was the longest fish oil trial ever conducted. Thus, we should not casually dismiss the findings of this trial.
A recent meta-analysis brought to light eleven trials that were placebo-controlled and lasted more than one year.80 Pooling the data from these studies together showed that fish oil reduced the relative risk of cardiovascular death by 13 percent and reduced the relative risk of all-cause mortality by 8 percent.
The Italian GISSI-Prevenzione and GISSI-Heart Failure trials were the largest included in this meta-analysis and were responsible for most of the effect. These trials, together with the DART 1 trial, suggested that fish oil may prevent arrhythmia in patients with chronic heart failure and patients who have recently survived a heart attack.81 Researchers provided participants with roughly one gram of long-chain omega-3 fatty acids per day. The GISSI trials found a long-term benefit over the course of almost four years in heart failure patients but a much shorter-term benefit concentrated in the first year of the study in patients who had recently undergone a heart attack. The DART 1 trial similarly found an early benefit of fatty fish consumption and fish oil supplementation in patients who had recently suffered from a heart attack. Fish oil thus seems likely to prevent very specific types of heart failure rather than to prevent heart disease more generally.
None of these trials provided any evidence that healthy people benefit from taking fish oil or that doses higher than one gram of omega-3 fatty acids per day provide any benefit over smaller doses. The results of the DART 2 trial are particularly concerning because, like the results of the Wadsworth Veterans Administration Hospital Study (see sidebar on page 29), they suggest that high intakes of PUFAs may increase the risk of morbidity and mortality when consumed over the course of many years.